Construction of lncRNA-miRNA-mRNA network based on ceRNA mechanism reveals the function of lncRNA in the pathogenesis of gout.
Construction of lncRNA-miRNA-mRNA network based on ceRNA mechanism reveals the function of lncRNA in the pathogenesis of gout.
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基于ceRNA机制构建lncRNA-miRNA-mRNA网络揭示lncRNA在痛风发病机制中的功能
DOI：
10.1002/jcla.24451
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发表时间：
2022-06
影响因子：
2.7
通讯作者：
Li, Huanan
中科院分区：
文献类型：
--
作者：
Chen, Feng;Zhang, Xiaoyun;Chen, Yueping;Chai, Yuan;Jiang, Xiao;Li, Huanan
鉴定痛风发病过程中lncRNA、miRNA、mRNA的差异表达，探索痛风的ceRNA网络调控机制，寻找潜在的治疗靶点。首先，通过GEO数据库检索痛风相关芯片。然后，通过R语言等软件对差异表达的lncrna和mrna进行分析。此外，基于公共数据库预测miRNA及其调控mRNA，取差异表达mRNA与预测mRNA的交集，获得lncRNA‐miRNA‐mRNA调控关系，构建ceRNA调控网络。随后，利用STRING数据库和Cytoscape软件筛选枢纽基因。然后利用DAVID数据库阐明枢纽基因的基因功能和相关通路，挖掘关键的ceRNA网络。388个lncrna和758个mrna在痛风患者中有显著差异表达，它们调节ceRNA网络中的中枢基因，如JUN、FOS、PTGS2、NR4A2和TNFAIP3。在ceRNA网络中，lncRNA与mRNA竞争miRNA，通过调节细胞对化学应激的反应，影响IL - 17信号通路、TNF信号通路、催产素信号通路和NF - κB信号通路。研究表明，5种mirna （miR‐429、miR‐137、miR‐139‐5p、miR‐217、miR‐23b‐3p）和5种lncrna （SNHG1、FAM182A、SPAG5‐AS1、HNF1A‐AS1、UCA1）在痛风的形成和发展中发挥重要作用。ceRNA网络的相互作用可以通过调节机体的炎症反应以及软骨细胞和破骨细胞的增殖、分化和凋亡来影响痛风的形成和发展。通过ceRNA网络发现潜在的治疗靶点和信号通路，可为进一步研究痛风发病机制提供参考。
To identify differentially expressed lncRNA, miRNA, and mRNA during the pathogenesis of gout, explore the ceRNA network regulatory mechanism of gout, and seek potential therapeutic targets. First, gout‐related chips were retrieved by GEO database. Then, the analysis of differentially expressed lncRNAs and mRNAs was conducted by R language and other software. Besides, miRNA and its regulated mRNA were predicted based on public databases, the intersection of differentially expressed mRNA and predicated mRNA was taken, and the lncRNA‐miRNA‐mRNA regulatory relationships were obtained to construct the ceRNA regulatory network. Subsequently, hub genes were screened by the STRING database and Cytoscape software. Then the DAVID database was used to illustrate the gene functions and related pathways of hub genes and to mine key ceRNA networks. Three hundred and eighty‐eight lncRNAs and 758 mRNAs were identified with significant differential expression in gout patient, which regulates hub genes in the ceRNA network, such as JUN, FOS, PTGS2, NR4A2, and TNFAIP3. In the ceRNA network, lncRNA competes with mRNA for miRNA, thus affecting the IL‐17 signaling pathway, TNF signaling pathway, Oxytocin signaling pathway, and NF‐κB signaling pathway through regulating the cell's response to chemical stress. The research indicates that five miRNAs (miR‐429, miR‐137, miR‐139‐5p, miR‐217, miR‐23b‐3p) and five lncRNAs (SNHG1, FAM182A, SPAG5‐AS1, HNF1A‐AS1, UCA1) play an important role in the formation and development of gout. The interaction in the ceRNA network can affect the formation and development of gout by regulating the body's inflammatory response as well as proliferation, differentiation, and apoptosis of chondrocytes and osteoclasts. The identification of potential therapeutic targets and signaling pathways through ceRNA network can provide a reference for further research on the pathogenesis of gout.
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DOI：
10.26355/eurrev_202011_23582
发表时间：
2020-01-01
影响因子：
3.3
作者：
Gao, S-T;Yu, Y-M;Lin, J-X
通讯作者：
Lin, J-X
影响因子：
3.4
作者：
Kawasaki, Hiromichi;Amano, Hirotaka
通讯作者：
Amano, Hirotaka
影响因子：
4.4
作者：
Hannemann, Nicole;Jordan, Jutta;Bozec, Aline
通讯作者：
Bozec, Aline
影响因子：
5.6
作者：
Miao C;Bai L;Yang Y;Huang J
通讯作者：
Huang J
影响因子：
--
作者：
Pearson, William R
通讯作者：
Pearson, William R